• MeSH
• chromozomální proteiny, nehistonové MeSH
• dítě MeSH
• infekce dýchací soustavy genetika   mortalita   MeSH
• jaderné proteiny MeSH
• kojenec MeSH
• konformace proteinů MeSH
• lidé MeSH
• mutace MeSH
• pneumonie genetika   mortalita   MeSH
• proteiny buněčného cyklu * fyziologie   genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH

BACKGROUND: Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. METHODS: Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. RESULTS: Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. CONCLUSIONS: HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

• MeSH
• bronchiální astma genetika   metabolismus   MeSH
• bronchiektazie genetika   metabolismus   MeSH
• bronchitida genetika   metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• cystická fibróza genetika   metabolismus   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• epitelové buňky metabolismus   MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mikro RNA metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pneumonie genetika   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• předškolní dítě MeSH
• protein CFTR genetika   MeSH
• proteiny genetika   metabolismus   MeSH
• respirační sliznice metabolismus   MeSH
• spirometrie MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• usilovný výdechový objem MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site.

• MeSH
• akutní nemoc MeSH
• akutní poškození plic komplikace   genetika   MeSH
• lipopolysacharidy MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• neutrofily patologie   MeSH
• peroxidasa nedostatek   genetika   MeSH
• pneumonie chemicky indukované   komplikace   genetika   MeSH
• poruchy leukocytů komplikace   genetika   MeSH
• vrozené poruchy metabolismu komplikace   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH